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Deep Dermatophytosis 2016-11-06 MMTN/Bangkok Pei-Lun Sun, MD Department of Dermatology Chang Gung Memorial Hospital, Linkou Branch Taoyuan, Taiwan Pei-Lun Sun, MD Superficial dermatophytosis Wikimedia Stratum corneum Tinea faciei Tinea corporis Tinea manuum Tinea cruris Tinea pedis Skin appendages Tinea capitis Tinea barbae Tinea ungiuum Pei-Lun Sun, MD Deep dermatophytosis Wikimedia Specific disease entity Majocchi’s granuloma / Trichophytic granuloma Dermatophytic pseudomycetoma Non-specific disease entity Deep dermatophytosis/ tinea profunda Invasive dermatophytosis Disseminated dermatophytosis Dermatophyte abscess + lymphadenopathy and/or angioinvasion + internal organ involvement Pei-Lun Sun, MD Deep dermatophytosis (1975-2016) • 79 cases • M:F = 56:23 • Age of disease onset: 8-83 y/o (39.8 ± 16.6) 18 16 14 12 10 8 6 4 2 0 0-9 10-19 20-29 30-39 40-49 50-59 60-69 70-79 80-89 ND Pei-Lun Sun, MD Clinical presentations Solid nodule(s) J Dermatol. 2004 Oct;31(10):839-43 J Am Acad Dermatol. 2004 Nov;51(5 Suppl):S173-6 Pei-Lun Sun, MD JAMA Dermatol. 2013 Apr;149(4):475-80 Plaques/papuloplaques Arch Dermatol. 2004 May;140(5):624-5 Mycopathologia. 2013 Dec;176(5-6):457-62 Mycoses. 2007 Mar;50(2):102-8 Am J Dermatopathol. 2011 Jun;33(4):397-9 J Clin Immunol. 2016 Apr;36(3):204-9 Pei-Lun Sun, MD Ulcerative N Engl J Med. 2013 Oct 31;369(18):1704-14 J Clin Immunol. 2015 Jul;35(5):486-90 Pei-Lun Sun, MD Clinical presentations Cystic masses/nodules J Am Acad Dermatol. 2006 Feb;54(2 Suppl):S11-3 Acta Derm Venereol. 2013 May;93(3):358-9 Pei-Lun Sun, MD BMC Infect Dis. 2016 Jun 17;16:298 Clinical presentations Lymphadenopathy Ann Dermatol Venereol. 2010 Mar;137(3):208-11 Pei-Lun Sun, MD Histopathology J Clin Microbiol. 2003 Nov;41(11):5298-301 Pei-Lun Sun, MD Mycopathologia. 2013 Dec;176(5-6):457-62 Histopathology Lymph node involvement Angioinvasion Clin Exp Dermatol. 2005 Sep;30(5):506-8 Med Mycol. 2010 May;48(3):518-27 Pei-Lun Sun, MD Risk factors • Chronic tinea • DM, hepatitis/liver cirrhosis, lymphoma/leukemia, HIV, hereditary hemochromatosis, ESRD, atopic dermatitis • Immunosuppressive Tx due to underlying disease: solid organ transplantation, myasthenia gravis, RA • Immunodeficiency: plasma factor deficiency, decreased T cell activity, CARD9 mutation Pei-Lun Sun, MD 18 16 14 Case number 12 10 8 6 4 2 0 Pei-Lun Sun, MD Pathogens 40 35 30 25 20 15 10 5 0 Pei-Lun Sun, MD Treatment • No treatment guideline is available now. • Systemic antifungal agent is always necessary. • Most commonly used drugs are fluconazole, itraconazole and griseofulvin, followed by terbinafine and amphotericin B. Ketoconazole, voriconazole, posaconazole have been used in a few cases. • Surgical excision: 10 cases (12.7%) 2% 7% 4% 12% 1 drug 2 drugs 3 drugs 75% 4 drugs 5 drugs Pei-Lun Sun, MD • Prognosis – Deep dermatophytosis confined to skin, without other organ involvement: all survived or died due to other cause not related to dermatophytes (N=47) – Invasive deep dermatophytosis with internal organ/LN involvement (N=32) • Resolved: 7 • Improved/partially resolved : 8 • Stabilized: 3 • Recurred: 2 • Died: 9 (due to invasive dermatophytosis) • Lost to follow up / not documented: 3 Pei-Lun Sun, MD Pathogenesis • Most cases of deep dermatophytosis had superficial dermatophytosis on body, which served as an source of infection, e.g. tinea corporis, tinea pedis, onychomycosis • Route of entry: follicular (ruptured of infected hair follicles) or non-follicular (trauma or direct invasion(?)) • Defects in host immunity: congenital or iatrogenic Mycopathologia. 2013 Dec;176(5-6):457-62 Pei-Lun Sun, MD J Clin Microbiol. 1996 Feb;34(2):460-2 Challenges on research of deep dermatophytosis • Low incidence: no randomized case control trial can be done • Diagnosis: histopathology and culture are essential • Disease terminology: not yet been clearly defined (prognosis) – Invasive, disseminated, generalized, systemic – Deep dermatophytosis / Majocchi’s granuloma / Pseudomycetoma • Complex pathogenesis: host immune background and pathogen characteristics An Bras Dermatol. 2014;89(5):839-40. Pei-Lun Sun, MD Conclusion • Deep dermatophytosis is a rare and invasive form of dermatophyte infection, which may lead to mortality. • An accurate diagnosis relies on skin biopsy for histopathology and fungal culture. • The host immune status play a major role in the disease pathogenesis, extend, and prognosis. • Systemic antifungal treatment is always necessary. • Superficial tinea should be properly managed before starting immunosuppressive treatment. Pei-Lun Sun, MD Thank you Pei-Lun Sun, MD .
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